Response predictors and clinical benefits of hepatitis C retreatment with pegylated interferon and ribavirin in HIV/HCV coinfection.

BACKGROUND: Hepatitis C is a leading cause of mortality among HIV-infected individuals. Therefore, eradication of HCV in this population is a priority. There are scarce data regarding retreatment efficacy of HIV/ HCV coinfected patients. The aim of our study was to evaluate efficacy, predictors of response, and long term clinical benefits of sustained virological response (SVR) after hepatitis C retreatment in a population of HIV/HCV coinfected patients. MATERIAL AND METHODS: We evaluated efficacy, safety, and clinical benefits of peginterferon(alfa-2a or alfa-2b) and ribavirin in a restrospective, observational, multicentric study, including 47 HIV/HCV coinfected patients, non-responders to previous treatment with conventional interferon alfa-2a and ribavirin. The primary endpoint of efficacy was SVR, defined as undetectable viral load 24 weeks after end of treatment. Death, liver disease progression, CD4 counts, and AIDS defining illness were the endpoints to access clinical benefits of treatment response. RESULTS: In our analysis, 31.9% patients reached SVR. Genotypes 2/3 had a significant better SVR (66.7%) compared to genotypes 1/4 (33.3%) (p = 0.022). During follow-up, deaths (6.89%) and hepatic decompensation (28.6%) occurred only in the nonresponder group, while there were no cases of death or hepatic decompensation among the responder group(p = 0.037). CONCLUSION: Nearly one third of patients (mainly those with genotypes 2/3) reached SVR after hepatitis C retreatment in this group of HIV/HCV coinfected patients. SVR was protective against hepatic decompensation and death in a two-year follow-up period. Retreatment may be an effective and safe way to eradicate HCV until new anti-HCV drugs become available to this group of patients.

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study.

INTRODUCTION: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. AIMS: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. METHODS: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. RESULTS: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with Peg-IFN and RBV were: absence of an AIDS-defining illness (p=0.001), HCV viral load lower than 600,000IU/mL at the onset of treatment (p=0.003), higher liver enzyme levels (p=0.039) at baseline, infection with genotypes 2 or 3 (p=0.003), and no transient treatment interruption (p=0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. CONCLUSIONS: in our Brazilian case series, the SVR rate under current clinical practice conditions was similar to that reported in other studies. There was a correlation between an SVR and being infected by genotypes 2 and 3, low viral load, high ALT levels at the onset of treatment, and absence of an AIDS-defining illness. Cytopenia and psychiatric disorders were the major causes of treatment interruption. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment.

The use of real-time PCR to detect hepatitis C virus RNA in dried blood spots from Brazilian patients infected chronically.

Collecting and transporting samples for RNA analysis can be challenging, especially in situations where financial resources are limited. In this study, a quantitative real-time PCR (qPCR) for the analysis of HCV RNA was developed and adapted for use with dried blood spot (DBS) samples. A qPCR for HCV 5'NCR, an internal control and a calibration curve were developed, and the sensitivity, specificity and dynamic range of amplification were evaluated using a panel of viruses. Plasma and DBS samples from 100 patients who had completed four weeks of Peginterferon alfa-2b+Ribavirin treatment were collected (DBS on SS903 collection cards and transported at room temperature). After 24 weeks of treatment, samples were collected from 68 of these patients. Of the 168 samples, 2 yielded false-negative results, and 4 yielded false-positive results (sensitivity was 98%, specificity was 94.3%, positive predictive value was 96.1%, and negative predictive value was 96.9%). Additionally, 2039 DBS samples from 1114 patients currently undergoing treatment for a chronic HCV infection in a clinical trial were tested. Only 10 samples out of the 2039 yielded invalid results warranting re-collection of DBS. The detection of HCV RNA in DBS can be a cost-effective strategy for HCV treatment monitoring, especially in settings where resources are limited.

Preenchimento facial com Polimetilmetacrilato em pacientes que vivem com a síndrome da imunodeficiência adquirida (AIDS) / Facial filling with polymethylmethacrylate in patients with acquired immunodeficiency syndrome

INTRODUÇÃO: Pacientes que vivem com síndrome da imunodeficiência adquirida (AIDS) em uso da Terapia Antirretroviral de Alta Potência (TARV) são suscetíveis a desenvolver síndrome lipodistrófica. O preenchimento facial com polimetilmetacrilato é opção de tratamento. O objetivo é analisar o procedimento de preenchimento facial e avaliar os pacientes em relação à percepção, incômodo, revelação do diagnóstico, expectativa quanto ao preenchimento e a satisfação e impacto em suas vidas. MÉTODOS: Análise em 63 pacientes submetidos ao preenchimento facial. Foram realizados procedimentos, analisados prontuários dos pacientes e o Protocolo do Ambulatório de Lipodistrofia do Programa Municipal de doenças sexualmente transmissíveis (DST)/AIDS e Hepatites Virais de São Bernardo do Campo, atendidos no período de janeiro a julho de 2009. RESULTADOS: Todos os 63 pacientes iniciais que concordaram em participar da pesquisa permaneceram até o término deste trabalho. Apenas seis pacientes (9,5%) eram de origem de outros municípios, enquanto 57 pacientes (90,5%) eram moradores de São Bernardo. 68,2% eram homens e 100% brancos. A média das idades foi 49,7 anos. Em média, o Vírus da Imunodeficiência Humana (HIV) foi diagnosticado há 11,5 anos, com tempo médio de uso de TARV por 10 anos e tempo médio de lipoatrofia facial de 3,8 anos. A maioria fez uso de Estavudina e/ou Efavirenz. Quem ficava mais desconfortável com as alterações na face eram os próprios pacientes. 85,7% não revelaram o diagnóstico para terceiros. 100% dos pacientes ficaram satisfeitos ou muito satisfeitos com o resultado obtido. CONCLUSÃO: 100% dos pacientes ficaram satisfeitos ou muito satisfeitos com o resultado obtido. Em 100% dos casos houve um impacto favorável na vida. Não houve efeitos adversos ao procedimento cirúrgico de preenchimento.

INTRODUCTION: Patients with acquired immunodeficiency syndrome (AIDS) who use highly active antiretroviral therapy (HAART) can develop lipodystrophy syndrome, for which facial filling with polymethylmethacrylate is a treatment option. The objective is to analyze the procedure of facial filling and evaluate patients in relation to their perception, discomfort, revelation of the diagnosis to third parties, expectation concerning facial filling, and satisfaction with the treatment outcome and its impact on their lives. METHODS: Sixty-three patients who underwent facial filling were evaluated. Procedures performed between January and July 2009 were assessed, the records of the patients were analyzed, and the outpatient lipodystrophy protocol of the STD/AIDS and Viral Hepatitis Municipal Program of São Bernardo do Campo was used. RESULTS: All the 63 patients who agreed to participate in the research completed the study. Only 6 patients (9.5%) were from other municipalities, while 57 patients (90.5%) were residents of São Bernardo. Of the patients, 68.2% were men and 100% were Caucasian. The mean age of the patients was 49.7 years. Human immunodeficiency virus was diagnosed 11.5 years prior on average, with 10-year average use of HAART and 3.8-year average time of facial lipoatrophy. Most of the patients used stavudine and/or efavirenz. The patients themselves felt more uncomfortable with facial changes. Among the patients, 85.7% did not reveal the diagnosis to third parties. CONCLUSION: All of the patients were satisfied or very satisfied with the result obtained, which had a favorable impact on their lives. The filling surgical procedure had no adverse effects.

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study

Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...